The Role of Wine in Modulating Inflammatory Processes: A Review
Abstract
:1. Introduction
2. Methods
3. Results and Discussion
3.1. In Vitro Methods
3.2. In Vivo Studies
3.2.1. Animal Studies
3.2.2. Human Studies
- The duration of the study, which could be too short to observe a significant change in inflammatory parameters in healthy subjects having physiological CRP levels (0.11–0.55 mg/dL) [28]. The study by Marfella et al. [42], seemed to support this hypothesis. Indeed, T2D patients, with a myocardial infarction history, consuming 118 mL wine/day in the previous 12 years showed CRP levels significantly lower when compared to abstainers (p < 0.01) [42];
- The amount of wine consumed (100–150 mL/day, 15 g ethanol) was lower when compared to studies where a CRP reduction was observed (>200 mL, 20 g ethanol) [36].
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Wine/Dosage | Model | Aim | Biomarkers | Method | Outcomes Showing Statistical Significant Changes | Ref. |
---|---|---|---|---|---|---|
Endothelial function | ||||||
RW (GAE 1, 10, 50 μg/mL) | HUVEC HMEC | To evaluate the vascular anti-inflammatory effects of two typical South Italy RWE (Primitivo and Negroamaro) and the specific contribution of each polyphenol | ICAM-1, VCAM-1 and E-Selectin, MCP-1, M-CSF, NF-κB, AP-1, Endothelial-monocyte adhesion | PCR ELISA | Both RW down-regulated the expression of adhesion molecules, ICAM-1, VCAM-1, E-Selectin, MCP-1, and M-CSF. The results were statistically significant starting from the lowest concentration (1 μg/mL) | [14] |
Gastric/intestinal function | ||||||
RW and DRW (GAE 50 μM) | Caco-2 | To assess the effects of wine on intestinal inflammation | IL-6, IL-8, ICAM, COX 2 | ELISA PCR | Only IL-6 was significantly reduced by RW and DRW (p < 0.05) | [15] |
PPE from RWE (200, 400, and 600 µg/mL) | HT-29 | To evaluate the potential anti-inflammatory action of RWE enriched in anthocyanins (25.9 mg/g) | IL-8, COX-2, NF-κB | ELISA | RWE reduced NF-κB, IL-8 and COX-2 production in a concentration-dependent manner | [16] |
PPE from RWE (200, 400, and 600 μg/mL) | HT-29 | To elucidate molecular mechanisms underlying the anti-inflammatory action of a PPE from Portuguese RWE | JAK/STAT and Nrf2 pathways | PCR | RWE significantly reduced the nuclear levels of phosphorylated STAT1 and the cellular levels of phosphorylated JAK1 induced by cytokines, suppressing the JAK/STAT inflammatory signaling cascade | [17] |
RWE Port Barrel Reserve prepared from LeNoir grapes (Vitis aestivalis hybrid) assayed at 25–100 μg/mL | Human colon-derived CCD-18Co myofibroblasts cells | To assess the chemopreventive potential of polyphenolics vs. the inflammation induced by external stimuli in human colon-derived CCD-18Co myofibroblasts cells. To assess the potential involvement of microRNA-126 (miR-126) in the previous mechanisms | NF-κB, ICAM-1, VCAM-1, and PECAM-1, TNF-α | PCR | RWE at 100 μg/mL GAE partially reversed the pro-inflammatory stimuli by inducing miR-126 This indicates the potential role of miR-126 in the anti-inflammatory properties of polyphenolics from red wine | [18] |
Wine/Dosage | Animal Model | Aim | Biomarkers | Method | Outcomes Showing Significant Changes | Ref. |
---|---|---|---|---|---|---|
Inflammation/Oxidative stress | ||||||
DRW (350 g/kg) from Spain or DWW (350 g/kg) for 15 days before carrageenan-granuloma induction | No. 21 adult male Sprague Dawley rats were divided into three groups: (1) control; (2) a 35% (v/w) DRW diet; (3) a 35% (v/w) DWW diet | To examine the effects DRW and DWW on carrageenan-granuloma induced inflammation | MDA, COX-2, iNOS expression, NO, O2- production by polymorphonucleate cells | MDA was measured by TBARS test; free radicals reduction was measured by ORAC assay; COX2 and iNOS expression was measured by electrophoresis and Immunoblotting using polyclonal antibodies | In both treated groups there was a decrease of MDA levels in plasma. In the same groups PMC showed decreased superoxide anion production and increased NO production; COX-2 was upregulated (pro-inflammatory effect) | [20] |
RW Syrah, Cabernet Sauvignon, and a blend from Chile, Brazil, and Argentina, respectively (alcohol content 12–13%). Total period: 4 weeks | No. 50 male Wistar rats divided in 5 groups: (1) control diet; (2) high fat diet + 770–1360 μL of water; (3) high fat diet + 800–1380 μL of RW with low antioxidant activity (LOW); (4) high fat diet + 790–1170 μL of RW with intermediate antioxidant activity (MED) or (5) 820–1340 μL of RW with high antioxidant activity (HIGH) | To evaluate the effect of wine on inflammation/oxidative stress induced by a high-fat diet | MDA (lipid peroxidation) Oxidative stress Antioxidant enzyme expression: superoxide dismutase, catalase, and GPx expression | MDA was measured by TBAR test; plasmatic antioxidant activity was measured by ORAC assay; expression of antioxidant enzymes was measured by electrophoresis | Groups supplemented with wines containing the highest antioxidant activity (HIGH) showed the lowest MDA concentration in liver tissue. All wines induced antioxidant enzyme expression | [21] |
Myocardial infarction | ||||||
WW (Grasevina Krauthaker vintage 2015, 13% alcohol) 5 mL/100 g bw for 4 weeks | 38 Sprague Dawley male rats (one month old) randomized into four groups: one group including animals drinking wine and three reference groups | To evaluate the effect of WW consumption on granulocyte and monocytes production 24 h after the surgically incflicted MI. This effect is positively correlated with tissue regeneration | CD15s, CD11b, and CD44, MMP-9 expression | Flow cytometry | White wine consumption caused a 3.2-fold (95% CI 1.569 to 3.86, p < 0.0001) increase in CD44 expression on monocytes in comparison to the water drinking controls. CD44 expression on granulocytes from wine group was slightly increased (p = 0.0203) in comparison to controls | [22] |
WW Grasevina Krauthaker vintage 2015, 13% ethanol) 6 mL/100 g bw For 4 weeks | 24 Sprague Dawley male rats randomized into 2 groups: control/water and wine | To investigate the effects of WW consumption on the expression of inflammatory mediators in myocardial tissue after induced myocardial ischemia | Three representative myocardial areas were identified and analyzed for inflammatory mediators (MMP-9, MMP-2, NF-κB, TG-β1) expression: infarct/ischemic, peri-infarct/border zone, and control/non-ischemic zones | Immunochemistry | MMP-9 were less expressed in all 3 zones of wine drinking animals (p < 0.001). MMP-2 expression was significantly decreased only in peri-infarctual zones (p < 0.001). Same pattern of expression was found for the NF-κB signal | [23] |
Gastric/Intestinal function | ||||||
MGE and MWE 500 mg/kg bw of mice for 14 days | 32 female C57BL/6J mice (8-week-old) randomly divided into four groups: (1) healthy mice (control) receiving water; (2) disease control group; (3–4) treated colitic mice | To determine the anti-inflammatory effects of phytochemical extracts on DSS-induced colitis in mice and to investigate cellular mechanisms. | IL-1β, IL-6, and TNF-α MPO activity | Mouse cytokine magnetic bead panel (immunochemical test) Spectrophotometric measurement | Phytochemicals from MGE or MWE mitigate ulcerative colitis via attenuation of pro- inflammatory cytokine production, modulation of the NF-κB pathway, and MPO activity. | [24] |
DRW 5 mL/mouse/day Total days 14 days, last 4 days treated with wine (treatment group) or water (control group) | BALB/c mice (6-week old average bw18 g) received daily two intragastric administrations of VacA | To investigate whether RW influences gastric inflammation in VacA-treated mice (toxin produced by H. pylori) | Alteration of gastric mucosa | Hystological examination of mucosal alterations and IHC staining using an antiVacA monoclonal antibody | The mucosal alterations were significantly milder in mice receiving RW vs. control mice. RW significantly prevented gastric epithelium damage in VacA-treated mice | [25] |
Metabolic syndrome | ||||||
Total period: 10 weeks; in the last 4 weeks animals were treated with RW. (Malbec) 35 mL/kg bw | No. 40 30-day old male Wistar rats were assigned to four groups: 1-water group (control), 2- F (10% fructose in drinking water), 3-F + E (10%fructose + ethanol 4.5 mL/kg), 4-F + RW (35 mL/kg containing 4.5 mL alcohol). | To evaluate the effects of moderate consumption of RW or ethanol on adiponectin, resistin expression, and vascular alterations in FFrs as an experimental model of MS. | Oxidative stress Adiponectin and resistin | Adiponectin, resistin, VCAM-1, and NF-κB protein expression were evaluated by WB analysis | RW administration to F rats was able to significantly decrease insulin resistance, mesenteric adipose tissue weight, and SbP compared to F group. F+RW reduced adiponectin expression decreased | [26] |
Cohort, Sample Size | Wine Intake/Duration | Aim | Biomarkers | Biomarkers Measurement | Outcomes | Ref. |
---|---|---|---|---|---|---|
Cardiovascular system | ||||||
38 healthy adults (wine consumers 61.44 ± 2.58 y; non-consumers: 60.73 ± 3.74 y) | Wine intake was assessed by annual frequency questionnaire | To bear out the association between the regular consumption of RW and some biomarkers of antioxidant status, lipid peroxidation, and inflammation | CRP | CRP human instant ELISA | No significant differences in CRP concentrations between RW consumers (mean intake = 100 mL) and non-consumers | [28] |
87 participants (mean age 50.2 ± 9.6 y) | Daily ingestion of one glass of RW/day (Cabernet Sauvignon, 150 mL, 15 g of alcohol) or total abstention. Intervention switch after 3 weeks with no wash-out | To study the acute effect of RW on the levels of the inflammatory markers | CRP, Fib | ELISA (CRP); Fib: Clauss’ assay (based on time for fibrin clot formation) | The consumption of 150 mL of RW slightly reduced Fib (3%) levels but did not reduce CRP levels in comparison with total abstention | [29] |
10 healthy men (mean age: 31.4 ± 4.3 y) | On four different days each subject consumed (with meals): 4 mL/bw of (1) WW (Robola variety), (2) RW (Cabernet Sauvignon variety); (3) ethanol solution (12,5% alcohol); (4) water 2-week wash out between treatments were requested | To evaluate the acute effect of wine consumption on platelet aggregation (T0–6 h after intake) | PAF, PAI-I | ELISA | At 150 min significant inhibition of platelet aggregation by RW (but not WW) vs. ethanol and water At 210 min platelet aggregation by RW vs. water | [30] |
12 healthy participants (mean age 31.3 ± 4.3 y) | In 4 different days each subject consumed (with meals): 4 mL/bw of (1) WW (Robola variety), (2) RW (Cabernet Sauvignon variety); (3) ethanol solution (12,5% alcohol); (4) water 2-week wash out between treatments were requested | To investigate the acute effect of wine consumption, on platelet aggregation and inflammation | PAF biosynthetic enzymes: Lyso-PAF AT and PAF-CPT, catabolic enzyme LpPLA2; IL-6 levels | Platelet aggregation assay [31]; ELISA | Both RW and WW decreased enzyme activity compared to ethanol. The protective effect of light to moderate wine (RW and WW) consumption could partly be explained through the modulation of PAF levels by decreasing their biosynthetic activities. No differences among treatments were observed on IL-6 level reduction | [32] |
83 participants (mean age 25.2 ± 1.1 y) | Participants were divided in 5 groups: (1) 264 mL RW; (2) 264 mL WW; (3) 633 mL of beer; (4) 79 mL whisky; (5) 264 mL water for 4 weeks | To examine the effect of acute administration of equivalent amount of alcohol (30 g) in different alcoholic beverages, on endothelial function and inflammatory processes (T = 4 h after intake) | IL-6, TNF-α, CRP, Fib, PAI-1, vWf, tPA | ELISA | Only RW and beer significantly improved endothelial function and decrease vWf levels, 4 h after consumption (p < 0.05 for both) vs. controls. In the same groups reactive hyperemia was significantly increased 1 h after (p < 0.05 for both), while it returned at baseline at 4 h. | [33] |
34 women (mean age 38 ± 8.5 y) | Participants were randomly assigned to two 4-week periods of 20 g ethanol/d as WW or RW (1 glass of 100 mL at lunch and at dinner), with two 4-week washout periods. | To investigate whether low intake of WW or RW has differential effects on inflammatory markers in women | hs-CRP, ICAM-1, VCAM-1, E-selectin, P-selectin, CD40L, IL-6 | hs-CRP: particle-enhanced IN; ICAM-1, VCAM-1, E-selectin, P-selectin, CD40L: ELISA | Both RW and WW reduced hs-CRP, ICAM-1, CD40L, IL-6 levels (p < 0.01) and CAMs expression by mononuclear cells (greater effect for RW). VCAM-1 and E-selectin decreased (p < 0.01) only in RW group. | [34] |
48 subjects (mean age 43.6 ± 10.6 y) | Participants were randomly assigned to two 4-week periods of Sicilian RW consumption (250 mL/d Nero d’Avola or 250 mL/d Etna Torrepalino-Solicchiata at meals), with 4-week washout periods. | To evaluate the effect of moderate RW consumption on some inflammatory biomarkers associated with cardiovascular risk factor | Plasma CRP, TGF-β1, D-Dimer, Factor VII, PAI Ag, tPA Ag, Fib, oxidized LDL Ab, TPAC | ELISA; ORAC assay for antioxidant activity | Both RW reduced Fib, factor VII, plasma CRP and oxidized LDL levels, while TGF-β1, tPA, PAI, and TPAC were significantly increased. | [35] |
40 healthy adult men (mean age: 37.6 ± 7.4 y) | Participants consumed two 160 mL glasses of RW (Merlot) or 100 mL gin (both 30 g of ethanol) for 28 days with 15 days wash out between treatments | To evaluate the effects of wine and gin on inflammatory biomarkers of atherosclerosis | LFA-1, VLA-4, MCP-1, VCAM-1, ICAM-1, IL-1α, hs-CRP and Fib | ELISA | Both gin and RW reduced plasma Fib and IL-1α levels. Only RW reduced serum concentrations of hs-CRP (−21%), VCAM-1 (−17%) and ICAM-1 (−9%). | [36] |
20 healthy adults (mean age 31.1 ± 0.8 y) | All participants smoked 3 cigarettes; n. 10 subjects consumed 1 h before smoking an amount of RW (Chateau Haut-Pontet) aiming to reach 0.075% blood alcohol content. | To evaluate whether RW consumption counteracts the adverse vascular effects of acute cigarette smoking. | IL-6, TNF-α, IL-1b expression, CD14, leukocytes | ELISA | Wine significantly reduced endothelial, platelet-, monocyte-, and leukocyte-derived microparticles (p < 0.001 each) and mRNA expression of IL-6, TNF-α, and IL-1b in monocytes vs. only smokers | [37] |
13 subjects with CAD (mean age 59.1 ± 7.0) | Participants received 4 mL/kg bw (2 to 3 glasses, corresponding to 0.52 g alcohol/kg bw) of RW (Stoneleigh Marlborough Pinot Noir) or WW (Jackson Estate Marlborough Sauvignon Blanc) at meals, with 1-week wash out between interventions. Three months after wine study, subjects received a non-alcoholic beverage 4 mL/kg bw at meals | To compare the acute effects of ingestion of RW and WW (T = 6 h after intake) on markers of inflammation in men with CAD. | IL-6, VCAM-1, ICAM-1 | ELISA | Acute RW and WW intake significantly increase plasma levels of IL-6 vs. non-alcoholic beverages | [38] |
Immune function | ||||||
27 healthy subjects (mean age 28 ± 6.3) | The study was performed in two parts: 1—Bolus study Participants received: 200 mL RW (Marienthaler Spatburgunder Klostergarten, 12% ethanol) (No. 9) or 200 mL DRW (Marienthaler Spatburgunder Klostergarten) (No. 9) or 200 mL water (No. 9) 2—Dietary intervention study (6-week) Subjects ingested 200 mL RW (n.27), 175 mL DRW (n. 26), water 200 mL (n. 25) 1 h after dinner | To evaluate effect of acute (T = 360 min after intake) and regular consumption (6 weeks) of wine on immunological parameters | T cell apoptosis, granulocytes, and monocytes phagocytosis | Annexin V fluorescein isothocyanate (FICT)/DNA-labeling flow-cytometry (Phagotest) | Only acute intake of RW decreased T cell apoptosis (p = 0.006 vs. p = 0.024 of controls). No other significant changes were observed among groups | [39] |
24 healthy non-smoking men (mean age 30.6 ± 1.4 y) | Subjects were randomly assigned to consume for 15 days 500 mL/day of RW (Lemberger, 12% ETOH v/v), DRW, RGJ (var Lemberger), and ETOH (12% ethanol v/v), with a wash-out period of 1-week between each experimental treatment | To investigate: (1) whether daily consumption of a moderate volume of RW modulates immune functions in healthy men in 2 weeks; (2) polyphenols in RW induce changes in immune functions vs. a 12% ETOH beverage. | Phagocytic activity of neutrophils and monocytes, production of TNFα, IL-2 and IL-4, TGF-β, expression of TNF-α mRNA, lymphocyte proliferation, lytic activity of NK cells, and percentage of apoptotic lymphocytes. | By flow-cytometry: lytic activity, phagocytosis and apoptosis by immunoassay: lymphocyte proliferation and cytokine secretion. | Consumption of a moderate volume of alcohol with RW and with a 12% ETOH, or RGJ had no effect on immune functions in healthy males. | [40] |
Type 2 diabetes | ||||||
24 T2D patients (mean age: 59.3 ± 1.1 y) and 22 healthy volunteers (mean age:54.1 ± 1.4 y) | Three study periods, each of 4-week (with no wash out): (1) RW (Shiraz Cabernet, 13% alcohol) (women: 230 mL/day men: 300 mL/day) at dinner; (2) DRW (Shiraz Cabernet (women: 230 mL/day men: 300 mL/day) at dinner; (3) Water | To examine the effects of RW on plasmatic SPMs, involved in promoting homeostasis after flogistic events | SPMs included: 18-HEPE, 17-HDHA, 14-HDHA, resolvins, and protectins | LC/MS-MS | RW did not differentially affect any of the SPMs measured in T2D patients when compared with DRW or water. | [41] |
Type 2 diabetes | ||||||
115 subjects with T2D with recent history of MI (mean age 35.5 ± 5.5 y) | Patients received 118 mL/day RW (Barbera, 11 g alcohol) with meals or not alcoholic beverages for 12 months | To examine the effects of moderate RW intake, with meals, on cardiac functions and inflammatory cytokine levels in T2D patients after MI | CRP, TNF-α, IL-6, IL-18 | Highly sensitive, quantitative sandwich enzyme assay CRP: IN | RW in the intervention group significantly reduced pro-inflammatory cytokines CRP, TNF-α, IL-6, IL-8 vs. control group | [42] |
801 participants (68.5 ± 7.2 years) | Subjects were classified as non-consumers (no consumption of alcohol-containing beverages including wine); moderate consumers and high consumers (men: ethanol intake >20 g/d; women: ethanol intake >10 g/d). | To investigate the association between wine consumption and endothelial dysfunction and low-grade inflammation | Endothelial dysfunction was evaluated using Z-scores (higher scores indicate worse function) for: vWf, sE-selectin, sTM, sVCAM-1 and sICAM-1, low-grade inflammation: CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1 | Multiarray detection system based on ECL technology vWf: ELISA | Wine consumption was associated with a lower endothelial dysfunction vs. wine abstention but not vs. alcohol intake | [43] |
Area | Wine Amount | Results | Ref. | |
---|---|---|---|---|
In vitro studies | Cardiovascular | 1–25 μmol/L GAE RW | ↓endothelial adhesion molecules | [14] |
Intestinal (Caco2) | 8.51 μg/mL GAE RW | ↓IL-6 | [15] | |
Intestinal (H29) | 100–600 μg/mL GAE RW | ↓IL-8 and ↓COX2 | [16,17] | |
Intestinal (Colon-derived CCD-18Co myofibroblast cells) | 25–100 μg/mL GAE RW | ↓VCAM-1 | [18] | |
Area | Wine amount | Results | Ref. | |
Animal studies | Cardiovascular (rats) | 50 mL/kg bw WW for 4 weeks | ↑CD44 expression; ↓MMP-9 expression | [22,23] |
35 mL/Kg bw RW for 4 weeks | ↓adiponectin, ↓resistin, ↓VCAM-1 and ↓plasmatic antioxidant activity | [26] | ||
Gastric/Intestinal (mice) | 250 mL/kg bw/day RW 4 days | ↓epithelial gastric damage | [25] | |
↓MPO levels | [24] | |||
Inflammation (rats) | 28 mL/Kg bw DRW and DWW for 15 day | ↓Oxidative stress (RW) ↓MDA (RW and WW) | [20] | |
3.6 mL/Kg bw RW 4 weeks | ↓MDA | [21] | ||
Human studies * | Cardiovascular (Healthy subjects) | 1.4 mL/kg bw RW 12 months | ↓MDA | [28] |
2.1 mL/kg bw RW 3 weeks | ↓Fib | [29] | ||
4 mL/kg bw day RW and WW, single dose | ↓PAF, ↓E-selectin, ↓ICAM, ↓TNF-α, ↓IL-6, ↓IL-8, ↓CRP | [30,32,33] | ||
2.9 mL/kg bw day RW and WW for 4 weeks each | [34] | |||
RW aiming to reach 0.075% blood alcohol in occasional smokers | ↓IL-6, ↓TNF-α, ↓IL-1b | [37] | ||
Cardiovascular (CAD patients) | 4 mL/kg bw, single dose | ↑IL-6 | [38] | |
Type 2 diabetes | >0–<20 g/day 0–<2.9 mL/kg bw | ↓inflammatory parameters | [43] | |
1.69 mL/kg bw RW for 12 months | ↓inflammatory parameters | [42] | ||
3.8 mL/kg bw RW or DRW for 4 weeks each | No effects | [41] | ||
Immune function | 2.50 mL/kg bw RW single dose; 7.14 mL/kg bw RW for 2 weeks | No effects | [39,40] |
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Di Lorenzo, C.; Stockley, C.; Colombo, F.; Biella, S.; Orgiu, F.; Dell’Agli, M.; Restani, P. The Role of Wine in Modulating Inflammatory Processes: A Review. Beverages 2018, 4, 88. https://doi.org/10.3390/beverages4040088
Di Lorenzo C, Stockley C, Colombo F, Biella S, Orgiu F, Dell’Agli M, Restani P. The Role of Wine in Modulating Inflammatory Processes: A Review. Beverages. 2018; 4(4):88. https://doi.org/10.3390/beverages4040088
Chicago/Turabian StyleDi Lorenzo, Chiara, Creina Stockley, Francesca Colombo, Simone Biella, Francesca Orgiu, Mario Dell’Agli, and Patrizia Restani. 2018. "The Role of Wine in Modulating Inflammatory Processes: A Review" Beverages 4, no. 4: 88. https://doi.org/10.3390/beverages4040088